Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

AtT20 cells, a line of murine pituitary tumour cells that secrete adrenocorticotropic hormone (ACTH), have been infected with the coronavirus mouse hepatitis virus strain A59 (MHV-A59). Between 5% and 10% of AtT20 cells are susceptible to the infection. Unlike infections of fibroblastic sac- and 17Cl 1 cells, the infection of AtT20 cells does not lead to cell fusion, despite the production of the fusogenic E2 viral spike glycoprotein. Within infected AtT20 cells the second viral envelope glycoprotein, E1, is located in a perinuclear region; at least until very late in the infection it fails to accumulate to detectable levels in the rough endoplasmic reticulum (RER). By contrast to infection of sac- and 17Cl 1 cells, where the RER is a major site of assembly of progeny virions, in AtT20 cells budding of progeny virions is restricted to the Golgi cisternae, which eventually vesiculate, and peri-Golgi smooth membraned vesicles. Apparently, therefore, the intracellular compartments into which wild-type MHV-A59 buds are determined not by the virus but by the host cells. MHV-A59 infected cultures of AtT20 cells can be serially passaged without loss of the infection or increase in the proportion of infected cells; they become persistently infected carrier cultures. The progeny virus from serially passaged, infected AtT20 cells is apparently wild-type. It infects sac- cells and induces them to form syncitia. Within the sac- syncitia the viral E1 glycoprotein accumulates in the RER and many virions assemble there.
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PMID:Infection of AtT20 murine pituitary tumour cells by mouse hepatitis virus strain A59: virus budding is restricted to the Golgi region. 299 76

Genetically obese mice (C57BL/6J-ob/ob), fed ad libitum, demonstrated a precipitous increase in the spontaneous death rate after 50 weeks. The first signs of morbidity were a ruffled hair coat and a progressive motor ataxia. Necropsy revealed that obese mice had pale and fatty livers, urolithiasis and grossly distended bladders. Microscopically, the hepatocellular changes observed in all aged obese mice included: a loss of orientation of hepatocytes, an enormous variability in the size of both hepatocytes and their nuclei, and an extensive deposition of both large and small lipid droplets, confirmed by an increase content of triacylglycerols. A subacute-to-chronic, multifocal, necrotizing hepatitis was also present. Kidneys from aged obese mice contained hypertrophied glomeruli and increased PAS-stained material. Tubular dilation with compaction of the tubular cells was also seen. There were no significant alterations in the microanatomy or mineralization of femurs from obese mice, yet there was a significant increase in plasma alkaline phosphatase activity. In obese mice at 62-63 weeks of age, hyperglycemia was present even in spite of hyperinsulinemia. Pituitary immunoreactive ACTH and its molar ratio to pituitary immunoreactive beta-endorphin were also increased in obese mice at this age. Even though the etiology of the decreased lifespan of genetically obese mice remains uncertain, the possibility is discussed that an overall defect in the central nervous system may be involved.
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PMID:Hormonal, metabolic and morphologic studies of aged C57BL/6J obese mice. 673 67

Seventy-two long-surviving liver transplant recipients were evaluated prospectively, including a baseline allograft biopsy for weaning off of immunosuppression. Thirteen were removed from candidacy because of chronic rejection (n = 4), hepatitis (n = 2), patient anxiety (n = 5), or lack of cooperation by the local physician (n = 2). The other 59, aged 12-68 years, had stepwise drug weaning with weekly or biweekly monitoring of liver function tests. Their original diagnoses were PBC (n = 9), HCC (n = 1), Wilson's disease (n = 4), hepatitides (n = 15), Laennec's cirrhosis (n = 1), biliary atresia (n = 16), cystic fibrosis (n = 1), hemochromatosis (n = 1), hepatic trauma (n = 1), alpha-1-antitrypsin deficiency (n = 9), and secondary biliary cirrhosis (n = 1). Most of the patients had complications of long-term immunosuppression, of which the most significant were renal dysfunction (n = 8), squamous cell carcinoma (n = 2) or verruca vulgaris of skin (n = 9), osteoporosis and/or arthritis (n = 12), obesity (n = 3), hypertension (n = 11), and opportunistic infections (n = 2). When azathioprine was a third drug, it was stopped first. Otherwise, weaning began with prednisone, using the results of corticotropin stimulation testing as a guide. If adrenal insufficiency was diagnosed, patients reduced to < 5 mg/day prednisone were considered off of steroids. The baseline agents (azathioprine, cyclosporine, or FK506) were then gradually reduced in monthly decrements. Complete weaning was accomplished in 16 patients (27.1%) with 3-19 months drug-free follow-up, is progressing in 28 (47.4%), and failed in 15 (25.4%) without graft losses or demonstrable loss of graft function from the rejections. This and our previous experience with self-weaned and other patients off of immunosuppression indicate that a significant percentage of appropriately selected long-surviving liver recipients can unknowingly achieve drug-free graft acceptance. Such attempts should not be contemplated until 5-10 years posttransplantation and then only with careful case selection, close monitoring, and prompt reinstitution of immunosuppression when necessary.
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PMID:Weaning of immunosuppression in long-term liver transplant recipients. 783 42

Met-enkephalin is known to circulate in human and animal plasma in low levels. However, the source(s) of plasma met-enkephalin have not been completely elucidated. It has been proposed that the adrenal gland, sympathetic nerves, pancreas and the gut might be implicated. Recently, markedly elevated levels of met-enkephalin have been documented in the presence of liver disease. To investigate potential sources of met-enkephalin in liver disease, rats with acute cholestatic hepatitis 24 h after gavage with alpha naphthylisothiocyanate (ANIT) 100 mg/kg were studied. Plasma met-enkephalin levels were determined by radioimmunoassay in plasma samples from normal, adrenalectomized, or chemically sympathectomized animals. In control rats, ANIT treatment resulted in a striking 8.7-fold increase in systemic venous met-enkephalin levels (inferior vena cava) (P < or = 0.0005) and a significant increase in peptidase-derived met-enkephalin levels (determined after trypsin/carboxypeptidase B digestion of plasma samples) (P < or = 0.05). ANIT-treatment also resulted in a 5.6-fold increase in portal vein met-enkephalin levels (P < or = 0.005). Portal vein met-enkephalin levels were only 1.2-fold higher than IVC levels in ANIT-treated rats (P < or = 0.05). Plasma activities of the two main enkephalin degrading enzymes, aminopeptidase and enkephalinase, were similar in control and ANIT-treated rats. Chemical sympathectomy, prior to ANIT treatment, decreased the elevation in inferior vena caval met-enkephalin levels by 35% (P < or = 0.005). Adrenalectomy did not alter ANIT-induced increases in circulating met-enkephalin levels (pNS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sympathetic nerves, but not the adrenal gland, contribute to elevated plasma levels of met-enkephalin in rats with acute cholestatic hepatitis. 821 May 12

Recently, liver natural killer T (NKT) cells, which are specifically stimulated by alpha-galactosylceramide (alpha-GalCer), were found to play a critical role in intrahepatic immunity to several infections and certain hepatic disorders. However, the role of psychophysical stress on NKT cell-dependent liver injury induced by alpha-GalCer still remains to be elucidated. In this study, we employed inescapable electric foot shock as the mode of psychophysical stress and evaluated its effect on alpha-GalCer-induced hepatitis. Pre-exposure of 12 hours of foot shock stress before alpha-GalCer administration significantly enhanced alpha-GalCer-triggered increase in serum alanine aminotransferase levels, followed by increases in both liver caspase-3 activity and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive hepatocytes, thus indicating that the liver NKT cell-dependent apoptotic response was exacerbated by stress. Foot shock stress also significantly increased both the number of liver NKT cells and Fas expression levels on hepatocytes. Pretreatment with RU-486, a glucocorticoid (GC) receptor antagonist, completely reversed such stress-induced enhancement of the alpha-GalCer-triggered serum alanine aminotransferase and hepatocyte Fas antigen responses. In contrast, such a reversal effect was not found in the mice pretreated with naloxone, a micro-opioid receptor antagonist, which thus suggests that an elevation of endogenous GCs, but not beta-endorphin, as responsible for such stress-induced aggravation in mouse hepatitis models. In conclusion, foot shock stress-induced elevation of endogenous GCs exacerbates alpha-GalCer-initiated hepatic apoptosis through the expansion of liver NKT cells and the up-regulation of hepatocyte Fas antigen.
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PMID:Electric foot shock stress-induced exacerbation of alpha-galactosylceramide-triggered apoptosis in mouse liver. 1505 17

The Schmidt Syndrome (Type II Autoimmune-Syndrome) is characterised by an autoimmune adrenalitis in combination with a chronic lymphocellular thyreoiditis resulting in insufficiency of these organs in adulthood. Combination with diabetes is possible. The diagnosis is usually established by clinical examination and analysis of serum hormone levels (adrenocorticotropin hormone [ACTH], cortisol, thyroid stimulating hormone [TSH], triiodothyronine [fT3], thyroxine [fT4]). In the present case, initial diagnosis was rapid progressive liver failure of unknown origin with consecutive multiple organ dysfunction syndrome including dysfunction of heart, lungs, and kidneys. Frequent and less frequent causes of liver failure were ruled out, e.g. viral or autoimmune hepatitis, Budd-Chiari-syndrome, toxic, or drug induced liver failure. In retrospect, the multiple organ dysfunction syndrome was caused by hypoperfusion due to severe hypovolemia and hypoperfusion was induced by adrenocortical insufficiency proven by endocrinological testing. The clinical course of this case stresses the importance of the hormone balance in the critical ill patient. The guideline for treatment of patients with assumed hormonal dysregulation should include a full hormone status prior to substitution. The present case report also illustrates the importance of clinical signs and careful consideration of the medical history in detecting an autoimmune endocrine disease.
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PMID:Schmidt syndrome presenting as acute liver failure. 1566 98

Endogenous opioids participate in growth regulation. Liver regeneration relates to growth. Thus, we explored the expression of methionine enkephalin and of the delta opioid receptor 1 immunoreactivities with a polyclonal rabbit antibody in deparaffinized liver of patients with chronic liver disease. Fifteen of a total of fifty-eight samples expressed both opioid receptor and methionine enkephalin immunoreactivities, one sample expressed receptor but not methionine enkephalin immunoreactivity, and two samples expressed methionine enkephalin but not receptor immunoreactivity. Ten of the 45 (22%) samples from patients with chronic hepatitis C, four of the eight (50%) samples from patients with chronic hepatitis B, one of the five (20%) samples from patients with autoimmune hepatitis expressed both met-enkephalin and delta opioid receptor 1 immunoreactivities. The expression of methionine enkephalin and delta opioid receptor 1 immunoreactivities suggests that methionine enkephalin exerts an effect in situ, which may include regulation of liver regeneration. However, another possibility that concerns an effect of methionine enkephalin in the liver arises. As morphine, which acts via opioid receptors, has been reported to increase hepatitis C virus replication in vitro and to interfere with the antiviral effect of interferon, methionine enkephalin, analogous to morphine, may enhance the replication of the hepatitis C virus in the liver of patients with this type of viral hepatitis, and interfere with the therapeutic effect of interferon. These results may explain at least in part, why some patients with chronic hepatitis C infection do not respond to interferon therapy.
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PMID:Human hepatic met-enkephalin and delta opioid receptor-1 immunoreactivities in viral and autoimmune hepatitis. 1875 88